T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

Abstract

IntroductionChagas disease is a parasitic infection whose pathogenesis is related to parasite persistence and a dysfunctional cellular immune response. Variability in cytokine secretion among chronic Trypanosoma cruzi‐infected patients might preclude the identification of the pool of antigen specific T cells. The goal of this study was to determine the fraction of T cells responding to T. cruzi antigen measured by the expression of membrane TNF‐α and CD154.MethodsA total of 21 chagasic patients, 11 healthy and 5 non‐chagasic cardiomyopathy controls were analyzed. PBMCs were short‐term cultured in the presence of anti‐CD28, anti‐CD49d, anti‐TNF‐α, and TACE (TNF‐α converting enzyme) inhibitor either under T. cruzi‐lysate or polyclonal stimuli. Cells were stained with anti‐CD3, anti‐CD4, anti‐CD8, and anti‐CD154, and analyzed with flow cytometry.ResultsCD4+ and CD8+ T cells in chagasic patients displayed higher percentages of membrane‐bound TNF‐α+ and CD154+ compared with controls after T. cruzi‐antigen stimulation. Both markers displayed a positive correlation in the T cell subpopulations analyzed. Symptomatic chagasic patients were differentiated from asymptomatic patients based on the expression of CD154 and membrane TNF‐α in TCD4+ and TCD8+ compartments, respectively.ConclusionsThese results show that both markers could be useful for assessing the pool of antigen‐specific T cells in chronic chagasic patients.

An Animal Model of Acute and Chronic Chagas Disease With the Reticulotropic Y Strain of Trypanosoma cruzi That Depicts the Multifunctionality and Dysfunctionality of T Cells

“…Tissue injury has been suggested to be mediated by the immune response, which plays a decisive role in the development of chronic ChD (85). For instance, an association between TNF-α-producing cells and cardiac damage has been observed in the heart and plasma samples from patients with chronic ChD with cardiac complications (86, 87), and TNF-α production by T cells from patients with chronic ChD persists and is related to CD8 + T cell degranulation (88). Furthermore, patients with advanced-stage ChD disease exhibit a higher proportion of cytotoxic CD8 + T cells producing granzyme B and perforin than patients in early stages of the disease (25).…”

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

“…Nonetheless, it would not be the only mechanism, since IFN-γ knock-out mice exhibit a different phenotype than iNOS knock-out mice, the former presenting a more severe onset and resembling that of CD4 + and CD8 + double-deficient mutants ( 141 , 142 ). TNF-α has also been proven to be secreted by T. cruzi -specific CD8 + T cells isolated from Chagas disease patients ( 143 ). In addition, a reduction in the frequency of circulating CD8 + T cells in severe cardiac patients was observed in comparison with asymptomatic and mild cardiac patients, suggesting that CTL response might have a role in preventing the progression of the cardiac symptoms ( 144 ).…”

Percentages of CD4+CD8+ double-positive T lymphocytes in the peripheral blood of adults from a blood bank in Bogotá, Colombia

“…In this study, a higher expression of CD154 (CD40L) was found in CD4 low CD8 high cells. This activation marker has been used as an indicator for antigen-specific T-cell activation in CD4+ T-cells [27] and in CD8+ T-cells [28]. Remarkably, this DPT subpopulation has an effector memory phenotype [9,10].…”